Levels of ionizing radiation (x-rays and gamma rays), which have little effect on adult mammals, may permanently alter the developing fetus. As a result of experiments to date in fetal rats in which anterior pituitary cells were markedly enlarged in adult rats 4 months after fetal irradiation, the hypothalamic-pituitary axis is proposed as a sensitive target for radiation during late gestation. Rats received radiation exposures of 25, 50, 75 or 125 R on gestational day 15, after the period of major organogenesis. All doses altered pituitary cell morphology. The first aim of the proposed experiments is to determine the lowest dose of radiation which alters anterior pituitary cell morphology after gestational exposure of the Sprague-Dawley rat and then to determine the critical period for damage during gestation. Other endocrine glands (adrenal, thyroid and gonads) and hypothalamic areas will be studied in the same animals. Morphometric measurements of cell size and nuclear size will be made from light microscope sections. All changes will be confirmed with electron microscopy and will include changes in cytoplasmic structures. The second aim is to compare the effects of ionizing radiation with gestational exposure to an antithyroid compound (methimazole), an antiestrogen (clomiphen), an anticorticosteroid (metyrapone) and an antimitotic drug (6-mercaptopurine). It is expected that the target for ionizing radiation may be more precisely defined by these experiments. The adult rats in these experiments may be compensating functionally for the fetal exposure to radiation. However, the possibility is being investigated that doses to the fetus below 25 rad will cause permanent damage which can be detected by the above measurements.